Efficacy & Safety Study of Oral Aripiprazole in Adolescents With Schizophrenia (ATTAIN 266)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01149655
First received: June 22, 2010
Last updated: April 1, 2015
Last verified: April 2015
  Purpose

This will be a randomized, double-blind, placebo-controlled study consisting of a screening period, a conversion phase (Phase 1), a stabilization phase (Phase 2), and a double-blind maintenance treatment phase (Phase 3), and a follow up period.

Subjects may be either outpatients or inpatients between screening and through the time they reach stabilization at the end of Phase 2; hospitalization is not a study requirement. However, eligible subjects must be outpatients at the beginning of Phase 3.

Subjects will be assessed weekly during Phase 1, weekly for the first 4 weeks of Phase 2 and 3, and biweekly for the remaining weeks during each of Phases 2 and 3. Subjects will be encouraged to call the investigators with any exacerbation of psychotic symptoms and/or any tolerability issues. The investigator will also have the option to phone the subjects and their guardian(s) at any time to ensure clinical stability.

A data monitoring committee (DMC) will provide oversight for safety monitoring and reviewing the interim analysis. One interim analysis is planned after 75% of the total expected number of impending relapse events (28 events) are achieved and will be conducted by an independent data analysis center. The DMC will make a recommendation about stopping or continuing the study based on safety and efficacy reviews. The results of the interim analysis and individual subject data will remain blinded to the sponsor during the course of the study until the DMC determines that the study will conclude based on the results of the interim analysis, or the study is completed after 37 endpoint events.


Condition Intervention Phase
Schizophrenia
Drug: Aripiprazole
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Long-Term Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Aripiprazole (OPC 14597) as Maintenance Treatment in Adolescent Patients With Schizophrenia

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Overall Relapse Rate (in Percent) From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse. [ Time Frame: Baseline to Week 52/End of Phase 3 visit. ] [ Designated as safety issue: No ]
    The primary efficacy variable was overall relapse rate from randomization, as assessed by Clinical Global Impression of Improvement (CGI-I) score ≥5, Positive and Negative Syndrome Scale (PANSS) scores for hostility or uncooperativeness ≥5, or ≥20% increase in PANSS Total Score. Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score > 4 with an absolute increase of ≥ 2 on that specific item or absolute increase of ≥ 4 on the combined 4 PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content). OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Any suicidal behavior or answers of "yes" to Questions 4 or 5 on the suicidal ideation section of the C-SSRS OR 5) Violent or aggressive behavior resulting in clinically significant injury.


Secondary Outcome Measures:
  • Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria. [ Time Frame: Baseline to Week 52/End of Phase 3 visit. ] [ Designated as safety issue: No ]
    Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score > 4 with an absolute increase of ≥ 2 on that specific item or absolute increase of ≥ 4 on the combined 4 PANSS items. OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Any suicidal behavior or answers of "yes" to Questions 4 or 5 on the suicidal ideation section of the C-SSRS OR 5) Violent or aggressive behavior resulting in clinically significant injury.

  • Percentage of Responders in Each Treatment Group. [ Time Frame: Baseline to Week 52/End of Phase 3 visit ] [ Designated as safety issue: No ]
    Percentage of responders in each treatment group (i.e, response defined as meeting stability criteria). Participants stabilized on aripiprazole (trial drug) within the approved dose range of 10 to 30 mg/day and are tolerable based on clinical judgment.

  • Percentage of Participants Who Had Achieved Remission. [ Time Frame: Baseline to Week 52/End of Phase 3 visit. ] [ Designated as safety issue: No ]
    Percentage of participants who had achieved remission, where remission was defined as a score of ≤ 3 on each of the following specific PANSS items, maintained for a period of 6 months: delusions, unusual thought content, hallucinatory behavior, conceptual disorganization, mannerisms/ posturing, blunted affect, social withdrawal, and lack of spontaneity.

  • Percentage of Participants Who Discontinued Due to All Reasons Other Than Sponsor Discontinued Study. [ Time Frame: Baseline to Week 52/End of Phase 3 visit ] [ Designated as safety issue: No ]
    Percentage of participants discontinued due to all reasons other than sponsor discontinued study were noted.


Other Outcome Measures:
  • Mean Change From Baseline to Endpoint in PANSS Total Score. [ Time Frame: Baseline to Week 52/End of Phase 3 visit. ] [ Designated as safety issue: No ]
    The PANSS consisted of 3 subscales with a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicates (absence of symptoms) and a score of 7 indicates (extremely severe symptoms). The symptom constructs for each subscale were positive subscale, negative subscale and general psychopathology subscale. The PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

  • Mean Change From Baseline to Endpoint in CGI-S Score. [ Time Frame: Baseline to Week 52/End of Phase 3 visit. ] [ Designated as safety issue: No ]
    The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-s, the Investigator answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0= not assessed; 1= normal, not at all ill; 2= borderline mentally ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; and 7= among the most extremely ill participants.

  • Mean CGI-I Score at Endpoint. [ Time Frame: Baseline to Week 52/End of Phase 3 visit. ] [ Designated as safety issue: No ]
    Baseline for the double-blind maintenance phase was defined as the last visit with available data in the stabilization phase, and the CGI-I scale was completed prior to or on the first dose date in the double-blind maintenance phase. Response choices included: 0 = not assessed; 1 = very much improved,;2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; and 7 = very much worse.

  • Mean Change From Baseline to Endpoint in PANSS Positive Subscale. [ Time Frame: Baseline to Week 52/End of Phase 3 visit. ] [ Designated as safety issue: No ]
    The PANSS consisted of 3 subscales were a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated (absence of symptoms) and a score of 7 indicated (extremely severe symptoms). The 7 positive symptom constructs were delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

  • Mean Change From Baseline to Endpoint in PANSS Negative Subscale. [ Time Frame: Baseline to Week 52/End of Phase 3 visit. ] [ Designated as safety issue: No ]
    The PANSS consisted of 3 subscales were a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated (absence of symptoms) and a score of 7 indicated (extremely severe symptoms). The 7 negative symptom constructs were blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. The PANSS Total Score ranged from 30 (best possible outcome) to 210 (worst possible outcome).

  • Mean Change From Baseline to Endpoint in Children's Global Assessment Scale (CGAS). [ Time Frame: Baseline to Week 52/End of Phase 3 visit. ] [ Designated as safety issue: No ]
    The CGAS was developed by Schaffer and colleagues to provide a global measure of severity of disturbance in children and adolescents. The CGAS is a rating scale for evaluating the overall functioning of a participant during a specified time period on a continuum from psychological or psychiatric sickness to health. The CGAS is a valid and reliable tool for rating a child's general level of functioning on a health-illness continuum. CGAS score (range 1-100) was a single item score for rating a child's general level of functioning on a health-illness continuum, with higher scores represented better functioning.


Enrollment: 252
Study Start Date: July 2011
Study Completion Date: December 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1
Aripiprazole (2-mg, 5-mg, 10-mg, 15-mg, 20-mg, 25-mg or 30-mg)
Drug: Aripiprazole
Aripiprazole (2-mg, 5-mg, 10-mg, 15-mg, 20-mg, 25-mg or 30-mg)
Experimental: Phase 2
Aripiprazole (2-mg, 5-mg, 10-mg, 15-mg, 20-mg, 25-mg or 30-mg)
Drug: Aripiprazole
Aripiprazole (2-mg, 5-mg, 10-mg, 15-mg, 20-mg, 25-mg or 30-mg)
Placebo Comparator: Phase 3
Aripiprazole (10-mg, 15-mg, 20-mg, 25-mg or 30-mg) or placebo
Drug: Aripiprazole
Aripiprazole (10-mg, 15-mg, 20-mg, 25-mg or 30-mg)

  Eligibility

Ages Eligible for Study:   13 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with a current DSM-IV-TR diagnosis of schizophrenia, and a history of the illness (diagnosis or symptoms) for at least 6 months prior to screening.
  • Subjects who have shown previous response to antipsychotic treatment (other than clozapine) and are not resistant to treatment with other antipsychotics.
  • Subjects who are currently being treated with oral or depot antipsychotics other than clozapine.
  • Subjects with a history of relapse and/or exacerbation of symptoms when they are not receiving antipsychotic treatment.

Exclusion Criteria:

  • Subjects with a current DSM-IV-TR diagnosis other than schizophrenia.
  • Subjects with delirium, dementia, amnesia or other cognitive disorders; subjects with psychotic symptoms that are better accounted for by another general medical condition(s) or direct effect of a substance (i.e., medication, illicit drug use, etc.).
  • Subjects with attention deficit disorder or attention deficit hyperactivity disorder and/or subjects who were on a stimulant treatment for any period of time over the last one year prior to screening.
  • Subjects with any neurodevelopmental disorder, except Tourette's syndrome.
  • Subjects experiencing acute depressive symptoms within the past 30 days prior to screening.
  • Subjects who meet the DSM-IV-TR criteria for substance dependence (including alcohol and benzodiazepines, but excluding caffeine and nicotine) within the past 180 days prior to screening.
  • Subjects who have epilepsy, a history of seizures (except for a single childhood febrile seizure or post-traumatic seizure), or a history of severe head trauma or stroke, or have a history or current evidence of other unstable medical conditions.
  • Subjects with a history of subclinical hypothyroidism (TSH ≥ 4.0 mIU/L), known hypothyroidism or hyperthyroidism (unless the condition has been stabilized with medication for at least 90 days prior to entry into Phase 1 or Phase 2).
  • Subjects who have a medical history of uncontrolled diabetes, labile or unstable diabetes (brittle diabetes), newly diagnosed diabetes, or clinically significant abnormal blood glucose levels.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01149655

  Show 52 Study Locations
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Study Director: Eva Kohegyi, MD Otsuka Pharmaceutical Development and Commercialization, Inc.
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01149655     History of Changes
Other Study ID Numbers: 31-09-266
Study First Received: June 22, 2010
Results First Received: November 26, 2014
Last Updated: April 1, 2015
Health Authority: United States: Food and Drug Administration
Russia: Ministry of Health of the Russian Federation
Romania: National Agency for Medicines and Medical Devices
India: Drugs Controller General of India
Taiwan : Food and Drug Administration
Philippines: Bureau of Food and Drugs
Malaysia: Institutional Review Board

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Adolescent
Schizophrenia

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Aripiprazole
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on May 25, 2015